Gene expression profile by blocking the SYT-SSX fusion gene in synovial sarcoma cells. Identification of XRCC4 as a putative SYT-SSX target gene

Oncogene. 2003 Oct 23;22(48):7628-31. doi: 10.1038/sj.onc.1207153.


Increasing evidence suggests that the SYT-SSX fusion gene plays an important role in synovial sarcoma development and progression. However, very little is known about the downstream targets of SYT-SSX. In this study, we used antisense oligonucleotides to block the expression of the SYT-SSX fusion gene in synovial sarcoma cells. By comparing SYT-SSX inhibited cells with noninhibited cells, the gene expression profile was analysed using cDNA microarray and established by real-time PCR. Herewith, using a filter containing 1176 cancer-relevant genes, we found that the DNA repair gene XRCC4 and the DNA mismatch repair gene MSH2 were downregulated, whereas the gene encoding for the serine/threonine protein kinase PRK (also known as CNK), and the macrophage inhibitory cytokine MICI (also known as PLAB) were upregulated after the inhibition of SYT-SSX. In comparison, expression of the XRCC4 gene was undergoing the strongest alteration. Consistently, the protein expression of XRCC4 was found to be decreased after SYT-SSX inhibition, whereas there were no detectable changes for the other gene products. Our study provides some clues to elucidate the signaling pathways of the SYT-SSX fusion gene, as well as it demonstrates a valuable model system for search for other SYT-SSX targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MutS Homolog 2 Protein
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Sarcoma, Synovial / genetics*
  • Sarcoma, Synovial / metabolism*
  • Substrate Specificity
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • SYT-SSX fusion protein
  • XRCC4 protein, human
  • MSH2 protein, human
  • MutS Homolog 2 Protein